Mucin 1 (MUC1) is a membrane?bound, highly glycosylated protein that is overexpressed in all stages of malignant transformation. Overexpression of MUC1 together with loss of polarization and hypoglycosylation are associated with resistance to apoptosis, which is the process that results in efficient removal of damaged cells. Inhibition of the apoptotic process is responsible for tumor development, tumor progression and drug resistance. MUC1 is considered as an oncogenic molecule that is involved in various signaling pathways responsible for the regulation of apoptosis. Based on this, the aim of the present study was to discuss the involvement of MUC1 in the divergent mechanisms regulating programmed cell death.The clinical efficacy of colorectal tumor treatment is restricted due to platinum agent resistance. Translesion DNA synthesis (TLS) has been shown to contribute to this resistance; however, the exact molecular mechanism remains unknown. The present study aimed to investigate the possible function of the core of the TLS polymerase mitotic arrest deficient 2 like 2 (MAD2L2) in drug sensitivity, in order to provide a treatment rationale for platinum?based chemotherapy in colon cancer. In the present study, MAD2L2 was knocked down using MAD2L2?specific small interfering (si)RNA. HCT116 and SW620 cells were treated with oxaliplatin and MG132; oxaliplatin is a platinum compound that induces DNA damage and MG132 is a potent proteasome inhibitor. Cell viability was determined using an MTT assay. Cell apoptosis was examined via flow cytometry and TUNEL assay. The activity of proteasome 26S subunit, non?ATPase 13 (PSMD13) was detected using ELISA, while the expression levels of apoptotic?related proteins were detected via western blotting. The results demonstrated that cells treated with oxaliplatin or MG132 alone had decreased viability, but a synergistic effect was not observed after co?treatment. In addition, the knockdown of MAD2L2 caused by siMAD2L2 or oxaliplatin treatment increased the expression levels of the pro?apoptotic proteins Bax and Bak and decreased the expression levels of the anti?apoptotic protein Bcl?2, compared with the negative control group. Moreover, MG132 alleviated the decrease in MAD2L2 expression, while reducing siMAD2L2?induced cell apoptosis. These results indicate that oxaliplatin promotes siMAD2L2?induced apoptosis in colon cancer cells. This process was associated with the Bcl?2 and ubiquitin?proteasome pathway. Overall, the present study provides a theoretical basis for improving the clinical efficacy of colon cancer by combining chemotherapy and gene therapy.Previous studies have identified microRNA (miRNA/miR)?3613?3p as a heat stress (HS)?related miRNA in endothelial cells that can lead to apoptosis. https://www.selleckchem.com/products/sch772984.html However, the mechanism underlying the miR?3613?3p?mediated apoptosis of HS?exposed endothelial cells remains unclear. In the present study, western blot analysis and reverse transcription?quantitative PCR were used to determine protein and miRNA expression levels, respectively. Annexin V?fluorescein isothiocyanate/propidium iodide staining, caspase?3 activity measurements and DNA fragmentation assays were performed to detect apoptosis. To evaluate whether mitogen?activated protein kinase kinase kinase 2 (MAP3K2) was a direct target of miR?3613?3p, a luciferase reporter assay was performed. In addition, transient transfection was used to carry out loss? and gain?of?function experiments. The results revealed that miR?3613?3p expression was reduced in human umbilical vein endothelial cells (HUVECs) following HS, which led to apoptosis. Mechanistically, following HS, a decrease in miR?3613?3p binding to the 3'?untranslated region of MAP3K2 directly upregulated its expression, and the downstream p38 and caspase?3 pathways, thereby leading to apoptosis. Taken together, the results of the present study demonstrated that HS suppressed miR?3613?3p expression, which activated the MAP3K2/p38/caspase?3 pathway, leading to the apoptosis of HUVECs. In conclusion, the miR?3613?3p/MAP3K2/p38/caspase?3 pathway may serve an indispensable role in regulating the progression of apoptosis, indicating a regulatory role of miR?3613?3p in the pathophysiology of HS?exposed endothelial cells.Neutrophilic asthma (NA) is a subtype of asthma that responds poorly to corticosteroid treatment. In certain diseases, microRNA (miR)?29a?3p is considered to be a key regulatory molecule for remodeling of the extracellular matrix. However, the effect of miR?29a?3p on airway remodeling is unknown. The present study aimed to investigate the role of miR?29a?3p in NA. A mouse model of NA was established and these animals were compared to normal controls. Both groups of mice were subjected to lung function tests and histopathological analysis. Human bronchial epithelial cells (16HBE) were grown in culture and incubated with secreted protein acidic rich in cysteine (SPARC) and a miR?29a?3p mimic. The expression of miR?29a?3p, SPARC and epithelial?mesenchymal transition (EMT)?related markers were measured using reverse transcription?quantitative PCR and western blotting. Luciferase reporter assay was performed to identify the direct regulatory relationship between miR?29a?3p and SPARC. miR?29a?3p expression was significantly decreased, while SPARC expression was increased in the NA mouse model with a phenotype of EMT. Overexpression of SPARC downregulated the expression of E?cadherin, while it increased the expression of vimentin in 16HBE cells. miR?29a?3p administration reversed the SPARC?induced effects on E?cadherin and vimentin expression. Luciferase assays confirmed that SPARC was the target gene for miR?29a?3p. Furthermore, SPARC overexpression increased the protein expression of phosphorylated (p)?ERK, while transfection with miR?29a?3p mimics significantly inhibited this increase. The data suggested that EMT in the NA mouse model was associated with decreased levels of miR?29a?3p and elevated SPARC. Furthermore, SPARC could induce the formation of EMT in 16HBE cells in vitro and this was directly targeted by miR?29a?3p and mediated by p?ERK, suggesting that miR?29a?3p may participate in the airway remodeling of NA.